Continuous-flow systems of the type shown in the L. T. Skeggs, U.S. Pat. No. 3,241,432, issued on Mar. 22, 1966, and assigned to a common assignee, provide for the quantitative analysis of biological samples. Such systems generally contemplate passing a plurality of liquid segments successively as a continuous stream along a conduit, each sample segment being segmented and interdigitated by air or other inert fluid segments. Such segmentation pattern assists in intramixing the individual sample segments and maintains a uniform flow pattern. The air segments reduce contamination between successive sample segments by preventing carryover, i.e., contamination of successive sample segments by residues from a preceding sample segment remaining on the conduit wall. The air segments serve to scrub the walls of the conduit clean of these residues, so as to reduce carryover. In addition, a wash liquid segment is introduced between successive sample segments, so as to further reduce the possibility of contamination therebetween.
In prior art continuous-flow systems, introduction of diluent and/or reagents to the sample stream is generally achieved by the confluence of the sample stream with a continuously flowing diluent and/or reagent stream. As a result, reagent and/or diluent are introduced into portions of the continuous stream other than the sample segments and, hence, are wasted. In addition, the presence of many segments of both air, wash liquid and sample increases the processing time of the successive samples. Also, the basic operability of these continuous-flow systems requires that each analyte in a sample be analyzed in a separate channel, i.e., a plurality of analytical channels is required for multiple analyte testing.
In addition, these prior systems do not completely eliminate residue carryover, and rely on the scrubbing action of the air segments to clean the conduit wall of the leftover reagent.
In the blood-typing systems shown in the Peoples et al, U.S. Pat. No. 3,635,680, issued on Jan. 18, 1972, and assigned to a common assignee, a system is shown for reducing reagent uptake or consumption by introducing segments of different reagents in phased fashion and in fixed sequence, so as to merge with different segments of a same sample flowing in a continuous stream. While the system substantially reduces reagent consumption, it does not fully eliminate residue carryover or provide selectivity in respect of the analysis to be performed on each sample, i.e., the same tests are performed for each sample even if not required or desired. Thus, there is much waste and inefficiency in the processing of samples in this system.
In the W. J. Smythe et al, U.S. Pat. No. 3,479,141, issued on Nov. 18, 1969, and assigned to a common assignee, a continuous-flow system is described wherein carryover between successive samples in a continuously flowing stream is effectively eliminated. This system features encapsulation of the sample and air segments within an immiscible fluid. The immiscible fluid preferentially wets the interior surfaces of the conduit walls to the exclusion of the aqueous samples, thus completely eliminating residue carryover between successive samples. Reagents, however, are introduced in conventional fashion.
The present invention finds particular application in systems such as described in above-identified Smythe et al patent, to minimize reagent consumption by injecting a multiplicity of reagents, in precise controlled volumes and in a selected sequence, to any number of different segments of a same sample flowing in a continuous stream. The ability to selectively inject controlled volumes of different reagents into discrete sample segments moving along a conduit substantially minimizes reagent consumption. In addition, the variable (random) sequencing of the reagent injection coupled with introducing only that number of segments of each sample required for the desired analyses thereof allows for substantial increase in system throughput.